Functional properties of neuroglobin and cytoglobin. Insights into the ancestral physiological roles of globins
Functional properties of neuroglobin and cytoglobin. Insights into the ancestral physiological roles of globins
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DOI：
10.1080/15216540500037299
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发表时间：
2004-11-01
期刊：
影响因子：
4.6
通讯作者：
Weber, RE
中科院分区：
文献类型：
--
作者：
Fago, A;Hundahl, C;Weber, RE
脑红蛋白和细胞红蛋白是最近发现的两种脊椎动物球蛋白，它们分别在神经元组织和所有已研究的组织中低水平表达。基于它们的氨基酸序列，这些球蛋白似乎是遗传学上古老的，并且与其他脊椎动物球蛋白、肌红蛋白和血红蛋白相比，在进化过程中突变较少。与一些植物和细菌球蛋白一样，在没有外部配体的情况下，脑红蛋白和细胞球蛋白血红素是六配位的，因为血红素铁原子与近端和远端His残基都配位。虽然六配位球蛋白的生理作用在很大程度上仍不清楚，但脑红蛋白似乎参与细胞对缺氧的防御。我们目前的知识，脑红蛋白和细胞红蛋白的功能特性，并描述了一个数学模型来评估哺乳动物视网膜脑红蛋白的作用，在供应O-2供应的线粒体。如图所示，该模型反对神经红蛋白的这种重要作用，其更可能在抑制脑缺氧后产生的活性氧和氮物质方面发挥作用。细胞珠蛋白的O-2结合特性在缺氧时上调，这与该蛋白质在O-2需要反应中的作用一致，例如由羟化酶催化的反应。
Neuroglobin and cytoglobin are two recently discovered vertebrate globins, which are expressed at low levels in neuronal tissues and in all tissues investigated so far, respectively. Based on their amino acid sequences, these globins appear to be phylogenetically ancient and to have mutated less during evolution in comparison to the other vertebrate globins, myoglobin and hemoglobin. As with some plant and bacterial globins, neuroglobin and cytoglobin hemes are hexacoordinate in the absence of external ligands, in that the heme iron atom coordinates both a proximal and a distal His residue. While the physiological role of hexacoordinate globins is still largely unclear, neuroglobin appears to participate in the cellular defence against hypoxia. We present the current knowledge on the functional properties of neuroglobin and cytoglobin, and describe a mathematical model to evaluate the role of mammalian retinal neuroglobin in supplying O-2 supply to the mitochondria. As shown, the model argues against a significant such role for neuroglobin, that more likely plays a role to scavenge reactive oxygen and nitrogen species that are generated following brain hypoxia. The O-2 binding properties of cytoglobin, which is upregulated upon hypoxia, are consistent with a role for this protein in O-2-requiring reactions, such as those catalysed by hydroxylases.